Eosinophilic esophagitis (EE) is an emerging disease caused by dense infiltration of the esophageal epithelium by eosinophilic leucocytes. It is originated from local hypersensitivity to food or airborne allergens. Although the physiopathologic mechanisms of the illness have not been fully discovered, EE is a loss of immunologic tolerance by the esophagus, meaning that it should be considered as an active immunologic organ. In our study, we investigated the immunologic capacity of the epithelium using immunohistochemistry and stereology, to determine the cellular density of eosinophils, T and B lymphocytes, Langerhans cells, mast cells, and cells manufacturing immunoglobulin E in endoscopic biopsies of patients with EE (taken before and after topical treatment with fluticasone propionate) compared with normal individuals and patients suffering from gastroesophageal reflux disease (GERD). We have observed that the density of eosinophils in EE is 300 times greater than in normal conditions and it is only in this disease where eosinophils show signs of activation and degranulation (positivity to major basic protein immunostaining). The number of T intraepithelial lymphocytes also significantly rose in EE, compared with other entities, where CD8 cells were predominant. However, the human esophagus is deficient in B lymphocytes and we only found intraepithelial plasma cells that excreted immunoglobulin E in EE. Under normal conditions mast cells exist in the thickness of the epithelium that are slightly higher in GERD and multiply in density by 17 in EE. Langerhans cells did not show any significant variation in density under the different tested conditions. After topical treatment with steroids, the density of the different cell components fell to similar levels to GERD. Using our study, we can conclude that the human esophagus may contribute to the development of local immunologic responses as it contains all the necessary cell components. EE represents growth of this esophageal capacity and its pathogeny could respond to mixed cellular and humoral mechanisms.

Human testicular specimens were obtained from biopsies and autopsies covering the period from birth to adulthood. The number of testosterone-containing Leydig cells was determined using the peroxidase-anti-peroxidase method. This number decreased markedly from 3-6 months of age to the end of the first year of life and, up to 6 years of age, only a small number of testosterone-containing cells was found. From 6 years onwards the number of Leydig cells progressively increased. Ultrastructural examination revealed four types of Leydig cells: fetal-type Leydig cells (from birth to 1 year of age) with round nuclei, abundant smooth endoplasmic reticulum and mitochondria with tubular cristae; infantile-type Leydig cells (from birth to 8-10 years of age), showing a multilobated nucleus, moderately abundant smooth endoplasmic reticulum, some lipid droplets and mitochondria with parallel cristae; prepubertal, partially differentiated Leydig cells (from 6 years of age onwards) with regularly-outlined round nuclei, abundant smooth endoplasmic reticulum, mitochondria with tubular cristae, and some lipid droplets and lipofuscin granules; and mature adult Leydig cells (from 8-10 years of age onwards). The ultrastructure of the infantile-type Leydig cells and the lack of delay between the disappearance of the fetal-type Leydig cells and the appearance of infantile-type Leydig cells suggest that fetal-type Leydig cells give rise to the infantile-type Leydig cells. Before puberty, myofibroblast-like precursor cells differentiate into the prepubertal, partially differentiated Leydig cells, which complete their differentiation into the adult Leydig cells.

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Mast cells are a constant cell-type in the connective tissues of the human testis and epididymis from birth to adulthood. Ultrastructural study shows that these cells are similar to those found in other connective tissues. Histometric studies revealed that the number of mast cells in the interstitium, mediastinum and albuginea of the testis as well as in the epididymal connective tissue increases slightly during infancy, decreases during childhood, and then increases again at puberty. Increases at puberty are particularly evident in both the testicular interstitium and the epididymis. During adulthood, the number of mast cells progressively decreases in all testicular and epididymal connective tissues. Changes in mast cell number may be related to changes observed in the development of testicular connective tissue which occurs primarily during infancy and puberty.

In the hamster, male reproductive quiescence is accomplished via testicular atrophy and the germinal epithelium is regressed to spermatogonia and spermatocytes after 8-14 weeks of short photoperiods. However, the cellular mechanisms involved in this process have not been elucidated. As it is suggested that the regulation of seasonal testicular activity is characterized by coordinated shifts in the relationships between mitosis, meiosis and apoptosis, the changes in the proliferative and apoptotic activity in the seminiferous epithelium of photoinhibited Syrian hamster were examined and compared with those maintained in natural photoperiod. The proliferative activity was studied using BrdU immunostaining, and germ cell apoptosis was assessed by in situ TUNEL labelling and transmission electron microscopy. A significant increase in the rate of apoptosis (percentage of TUNEL-positive spermatogonia + spermatocytes) was observed in photoinhibited animals (2.84 +/- 0.16) compared with those exposed to natural photoperiod (0.77 +/- 0.03, p < 0.05). The majority of apoptotic germ cells were spermatocytes and in some occasions spermatogonia. Germ cell apoptosis was confirmed by morphological characteristics: condensation of the chromatin and nuclear fragmentation. The rate of proliferation (percentage of BrdU-positive spermatogonia + preleptotene spermatocytes) was significantly higher in photoinhibited hamsters (42.7 +/- 2.6) compared with animals exposed to natural photoperiod (31.1 +/- 1.6, p < 0.05). After the exposure to a short photoperiod the apoptotic index positively correlated with the proliferative index (r = 0.8150, p < 0.05). In conclusion, the seminiferous epithelium of photoinhibited Syrian hamsters is characterized by an increased rate of apoptosis associated to an enhanced rate of proliferation.

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The rise of mast cells density in the small bowel and mesenteric lymph node complex in rats with partial portal vein ligation suggests that these cells are involved in the etiopathogenesis of experimental portal prehepatic hypertensive enteropathy.

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+®) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+®. CSAT+® supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+® prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+® prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+® attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+® supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.